Risk factors of Middle East respiratory syndrome

29 December 2017

The ongoing battle against Middle East respiratory syndrome is the biggest infection control challenge throughout the region. However, the disease ranges greatly in severity, with some patients at far higher risk of death than others. Dr Anwar Ahmed, an associate professor at King Saud bin Abdulaziz University for Health Sciences, tells Abi Millar about the risk factors and discusses how they might inform healthcare strategy.

Since it first emerged in 2012, Middle East respiratory syndrome (MERS) has been a serious public health concern. As of November 2017, at least 2,102 people across 27 countries have contracted the infection, of whom 733 (around 35%) have died. Since the disease still has no vaccine or targeted treatment, controlling its spread is a challenge.

This applies, above all, in healthcare settings, where MERS infection is a very real concern. According to WHO, 31% of cases have been associated with transmission in a healthcare facility and there have been several large-scale outbreaks over the past few years.

The most recent of these occurred in Riyadh in June 2017, when a MERS-infected patient was brought to the emergency department of a city hospital. Since the patient did not know he had MERS, he came into contact with approximately 220 people, including healthcare workers, fellow patients and visitors. In total, 34 people were infected, and half were healthcare professionals. One of these patients subsequently visited a second healthcare facility, where five additional cases were identified.

It is clear, then, that current infection control measures are far from perfect. Despite maintaining a high state of vigilance, hospitals may fail to diagnose patients at an early stage of the illness or isolate them as necessary.

About nine out of ten patients reported with MERS-CoV tend to survive three days after diagnosis, and seven out of ten patients tend to survive 30 days after diagnosis.

“I think we need to increase public knowledge on the clinical factors of MERS, which may guide people towards early presentation and medical support,” says Dr Anwar Ahmed, an associate professor at King Saud bin Abdulaziz University for Health Sciences. “Identifying the clinical presentations could result in a better understanding of the virus, and prevent human-to-human transmission and hospital outbreaks.”

As a researcher in public health issues, Ahmed has taken an interest in MERS from the outset. The issue is particularly salient in Saudi Arabia – where he is based – while infections have been reported across the Middle East. Saudi Arabia has accounted for 82% of documented cases and an even higher proportion of fatalities.

Prevention control

While the route of transmission is not fully understood, many of these cases originate when humans come into contact with infected camels. For instance, the patient might have drunk raw camel’s milk or attempted to treat a sick animal. These kinds of practices recur despite official warnings; since 2014, the Saudi agriculture ministry has urged people who have regular contact with camels to “exercise caution and follow preventative measures”, such as washing their hands and using gloves.

Once a person contracts the MERS coronavirus (CoV), its presentation – and the prognosis – varies wildly. Although commonly associated with respiratory symptoms, including fever, cough, shortness of breath and pneumonia, it is sometimes very mild or even asymptomatic. At the other end of the spectrum, it can lead to respiratory failure and even death.

Ahmed’s most recent paper, published in the journal BMC Infectious Diseases in September, explores the factors most closely linked with MERS mortality. His goal was not just to establish the overall mortality rate, but also to determine why some groups of patients seem to fare so much better than others.

“There have been a number of studies in Saudi Arabia, but these show variability in reporting the mortality of MERS-CoV, ranging from 30–60%,” he says.

“Most of these studies are from a single centre or hospital – there is no national study that reports mortality in Saudi Arabia. This is why I decided to do a study that analysed data from the national Ministry of Health (MOH).”

By using data from the Saudi MOH website, Ahmed studied the 660 MERS-CoV patients who were reported between December 2014 and November 2016. This data contained basic demographic information, like age, gender and nationality, along with further details, such as the source of infection, whether they had a pre-existing illness, the severity of their infection and the date of death where relevant. He used a mathematical model to estimate overall mortality rates, as well as mortality three days after diagnosis and 30 days after diagnosis. These were found to be 29.8%, 13.8% and 28.3% respectively.

“About nine out of ten patients reported with MERS-CoV tend to survive three days after diagnosis, and seven out of ten patients tend to survive 30 days after diagnosis,” states Ahmed. “The study also identifies a number of factors that could impact the mortality at three and 30 days.”

Perhaps unsurprisingly, the first of these factors was age. Ahmed divided the patients into two groups, those over 60 and individuals under 60. Of the patients studied, 45.2% of the over-60s died, compared with just 20.0% of the under-60s. Interestingly, the sample was relatively old, with a mean age of 53.9 years. This may suggest that older people are more likely to become ill in the first place.

Gender did not appear to make too much of a difference to mortality, despite the fact that men were more vulnerable to the infection. The death rates among men and women were 31.2% and 27.1%, respectively – a statistically insignificant difference.

One thing that mattered was whether or not the patient was a healthcare worker. Of the 105 who contracted the virus, only two died from it, whereas mortality among the rest of the cohort stood at 35.0%. Ahmed thinks that the low mortality rate among hospital professionals may be due to early diagnosis and better infection control practices.

A final important factor was whether or not the patient had a pre-existing illness. Patients with an underlying condition were about twice as likely to die from the MERS virus, with just 42.9% of these patients surviving 30 days, compared with 82.8% in the rest of the sample. Unfortunately, the data did not differentiate between different types of comorbidity, making the situation hard to analyse further; it simply reported whether or not the patient had a pre-existing illness.

Recording the cases

“The data is just a summary, taken from the MOH website rather than hospital records, so there are no details of whether the patient had diabetes or heart disease, for example,” explains Ahmed. “This is one of the limitations of the study.”

Another limitation, he adds, is that the data was based on the date of diagnosis, rather than the date of symptom onset. Since not all patients experience MERS symptoms, and others experience them only mildly, the survival rates may be skewed slightly.

“We still need to do more research to understand the risk factors and the health outcomes of the patients,” he says. “We may also need to develop assessment tools to identify suspect cases at an early stage, in order to reduce the mortality rate.”

We need to develop a valid and reliable assessment tool to prevent future outbreaks, and to apply stricter control measures when treating patients at high risk of the infection.

These issues notwithstanding, Ahmed believes that the study has great strengths, and could be of value to policymakers and healthcare systems globally, helping to identify the patients most at risk of death from the illness. Above all, it could be useful to healthcare workers who are providing medical care for MERS patients.

“The study could serve as a guide for healthcare professionals when they monitor the spread of the virus in clinical settings,” he explains. “It could help them with early identification of patients at high risk of death, meaning they’re able to give these patients more support, along with early screening and other medical investigation. Early identifications could also help us to isolate specific patients in order to protect others from the infection.”

It is clear that more work needs to be done in this area. WHO, which continues to work with ministries of health in all affected countries, describes the continued occurrence of healthcare-associated outbreaks as “deeply concerning” and attributes the situation, in part, to the non-specificity of symptoms.

As its most recent fact sheet explains, “Enhancing infection prevention, and control awareness and implementation measures is critical to preventing the possible spread of MERS-CoV in healthcare facilities… It is important that all healthcare facilities establish and implement clear triage policies for rapid screening and assessment of potential MERS-CoV cases, and all cases with acute respiratory symptoms.”

Ahmed agrees that if we are to prevent future outbreaks, we will need a multilayered strategy.

“The most important thing is early detection of the virus via efficient diagnostic systems, and then immediate isolation of the patient,” he says. “Also, we need to develop a valid and reliable assessment tool to prevent future outbreaks, and to apply stricter control measures when treating patients at high risk of the infection. It’s also important to increase public awareness knowledge of MERS through education programmes and public policy.”

Although we are unlikely to eradicate the virus any time soon, it is clear that knowledge is power. Developing an awareness of the risk factors, as per Ahmed’s study, is an important step in the right direction.

In 2012, MERS was discovered in Saudi Arabia. Other countries with confirmed cases include Egypt, Iran, Qatar, Oman, Yemen and the UAE.

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